The Xenopus embryo's amenability to functional assays has made it one of the most productive model systems for biomedical research in the molecular era. Its high degree of conserved gene structure and function means that results from Xenopus can usually be applied to other vertebrates, such as human and mouse, while its experimental manipulability and unparalleled embryology allow rapid and direct characterization of gene activities. The worldwide Xenopus research community is large and growing, with increasing adoption of Xenopus tropicalis for conventional Ioss-of-function genetic experiments and other genomic approaches. Xenopus research has recently begun to be transformed by the application of reverse genetics, driven by the availability of sequence from a variety of EST and full-length cloning projects as well as the recent whole-genome shotgun sequence for Xenopus tropicalis. Over the next five years, using a well-established reverse genetic strategy, we will identify carriers of chemically-induced Xenopus tropicalis mutations in known genes at a rate of 35 loci per year, generating an international resource of null as well as hypomorphic alleles. In addition, for each gene we will provide a first-pass phenotypic analysis of predicted null alleles, including morphological screening, a standard set of in situ hybridisations, and transcriptional profiling using a small cDNA microarray. The establishment of this major resource will generate a high degree of synergy within the community, allowing the field to combine the full breadth of Xenopus functional approaches with previously unavailable defined genetic deficiencies, greatly contributing to our understanding of gene function in vertebrate development and disease.